Sclerosing Mesenteritis: Update on Rare GI Disease

Medscape

2 days ago

The American Gastroenterological Association (AGA) has issued an updated pragmatic review on sclerosing mesenteritis (SM). Published in Clinical Gastroenterology and Hepatology, the update evaluates available evidence for diagnosis and treatment and examines opportunities for future research in SM, previously known by such names as misty mesentery, mesenteric panniculitis, and inflammatory pseudotumor.
Led by Mark T. Worthington, MD, a professor of medicine in the Division of Gastroenterology and Hepatology at the University of Virginia in Charlottesville, Virginia, an expert AGA panel described SM as an uncommon benign idiopathic autoimmune disease of the mesenteric fat. Although of poorly understood etiology, gastroenterologists need to be prepared to diagnose it.
'CT radiologists increasingly are reporting SM and related lesions, such as misty mesentery,' Worthington told Medscape Medical News . 'We are also seeing new SM cases caused by immune checkpoint inhibitors in cancer treatment, and the oncologists ask us to manage this because it interferes with the treatment of the underlying malignancy. Those are often readily treated because we catch them so early.' Metabolic syndrome and associated conditions increase the risk for SM, as does aging.
The recent changes are intended to help clinicians predict disease activity and the need for other testing or treatment. 'For instance, most cases are indolent and do not require aggressive treatment — often no treatment at all — but for those that are aggressive, we want the clinician to be able to identify those and make sure the treatment is appropriate. The aggressive cases may warrant tertiary referral,' Worthington said. 'A secondary cancer is a possibility in this condition, so drawing from the SM radiology studies, we try to help the clinician decide who needs other testing, such as PET-CT or biopsy, and who can be monitored.'
As many as 60% of cases are asymptomatic, requiring no treatment. Abdominal pain is the most frequent symptom and its location on clinical examination should correspond to the SM lesion on imaging. Treatment involves anti-inflammatory medications tailored to disease severity and clinical response.
No biopsy is not necessary if the lesion meets three of the five CT criteria reported by B. Coulier and has no features of more aggressive disease or malignancy. Although some have suggested that SM may be a paraneoplastic syndrome, current evidence does not support this. SM needs to be differentiated from other diagnoses such as non-Hodgkin's lymphoma, peritoneal carcinomatosis, and mesenteric fibromatosis.
'There are now CT guidelines for who actually has SM, who needs a biopsy or a PET-CT to rule-out malignancy, and who doesn't,' said Worthington. 'Radiologists do not always use the Coulier criteria for diagnosis, but often they will with encouragement. From this review, a GI clinician should be able to identify SM on CT.'
Epidemiologically, retrospective CT studies have reported a frequency of 0.6%-1.1%, the panelists noted. And while demographic data are limited, a large early case series reported that SM patients had a mean age of 55 years and more likely to be men and of White race.
Patients with SM do not have a higher prevalence of autoimmunity in general, but may have increased rates of metabolic syndrome, obesity, coronary artery disease, and urolithiasis, the panelists noted.
The update allows room for differences in clinical judgment. 'For instance, a longer or more frequent CT surveillance interval can be justified depending on the patient's findings, and no one should feel locked in by these recommendations,' Worthington said.
Medical Therapy
Although there is no surgical cure, pharmacologic options are many. These include prednisone, tamoxifen, colchicine, azathioprine, thalidomide, cyclophosphamide, and methotrexate, as well as the biologics rituximab, infliximab and ustekinumab. Current corticosteroid-based therapies often require months to achieve a clinical response, however.
Bowel obstruction is managed nonoperatively when feasible, but medically refractory disease may require surgical bypass.
Offering his perspective on the guidance but not involved in its formulation, Gastroenterologist Stephen B. Hanauer, MD, a professor of medicine at Northwestern Medicine in Chicago, said, 'The most useful component of the practical review is the algorithm for diagnosis and determination when biopsy or follow-up imaging is reasonable in the absence of evidence.' He stressed that the recommendations are pragmatic rather than evidence-based 'as there are no controlled trials and the presentation is heterogeneous.'
Hanauer added that none of the recommended treatments have been shown to impact reduction on imaging. 'Hence, all of the treatments are empiric without biological or imaging endpoints.'
In his experience, patients with inflammatory features are the best candidates for immune-directed therapies as reduction in inflammatory markers is a potential endpoint, although no therapies have demonstrated an effect on imaging or progression. 'As an IBD doctor, I favor steroids and azathioprine or anti-TNF directed therapy, but again, there is no evidence beyond reports of symptomatic improvement.'
Worthington and colleagues agreed that treatment protocols have developed empirically. 'Future investigation for symptomatic SM should focus on the nature of the inflammatory response, including causative cytokines and other proinflammatory mediators, the goal being targeted therapy with fewer side effects and a more rapid clinical response,' they wrote.
Currently, said Worthington, the biggest gaps remain in treatment. 'Even the best studies are small and anecdotal, and we do not know the cytokine or other proinflammatory mediators.' In other comments, Gastroenterologist Eli D. Ehrenpreis, MD, research director, Internal Medicine Residency, at Advocate Lutheran General Hospital in Park Ridge, Illinois, and not involved in the update, found it fell short in several ways, including nomenclature. 'The appropriate term for this condition is mesenteric panniculitis, meaning inflammation of the mesenteric fat, seen histologically on biopsy. The term sclerosing mesenteritis introduces the idea of fibrosis, which is seen in a smaller number of patients, not all,' he told Medscape Medical News .
Ehrenpreis also took issue with the inclusion of the cancer drug tamoxifen as the most common treatment used. 'Mesenteric panniculitis, when it does not represent a malignancy, is a benign disease,' he said. 'However, many patients on tamoxifen will experience hormone-related adverse effects such as breast tenderness and hot flashes.' He noted the drug has an FDA Black Box warning for uterine malignancies, pulmonary embolism, and other thromboembolic events, including stroke. Another significant gap, in his view, is the lack of recognition of the psychological effects on patients of the diagnosis.
According to Ehrenpreis, more prospective analyses of treatments are needed with objective measures of success including symptom scoring and laboratory testing with erythrocyte sedimentation rate and C-reactive protein. 'And as with many rare diseases, a better understanding of the psychological effects of having a poorly understood disease and management of this challenge is vital to the comprehensive care of the patient with mesenteric panniculitis.'
This guidance was supported by the AGA.
Worthington reported renumeration from TriCity Surgery Center, Prescott, Ariz. The coauthor Wolf has received renumeration from AbbVie, Align Technology, Alnylam Pharmaceuticals, CVS Health ORP, Dexcom, Exact Sciences, HCA Healthcare, Johnson & Johnson, Eli Lilly, McKesson, Moderna, Regeneron Pharmaceuticals, Sarepta Therapeutics, Seagen, Stryker, and Thermo Fisher Scientific. Crockett has served as a consultant for IngenioRx. Pardi has served as a consultant for Boehringer Ingelheim and received research support from Atlantic, ExeGI Pharma, Rise Therapeutics, Janssen, Pfizer, Seres, Applied Molecular Transport, Takeda Pharmaceuticals, and Vedanta Biosciences.
Hanauer and Ehrenpreis had no conflicts of interest relevant to their comments.